Esketamine Intranasal

Reviewed on 4/28/2022

What Is Esketamine Intranasal and How Does It Work?

Esketamine Intranasal is a prescription medicine indicated, in conjunction with an oral antidepressant, for treatment-resistant depression (TRD) and major depressive disorder (MDD) in adults.

  • Esketamine Intranasal is available under the following different brand names: Spravato

What Are Dosages of Esketamine Intranasal?

Adult dosage

Solution, Intranasal: Schedule III

  • 28mg/device; each nasal spray device delivers 2 sprays that total 28mg
  • Available as a 56mg kit (two 28-mg nasal spray devices) or an 84mg kit (three 28-mg nasal spray devices)

Treatment-resistant Depression

Adult dosage

Induction phase

  • Weeks 1-4
    • Administer Intranasally twice per week
    • Day 1 starting dose: 56 mg
    • Subsequent doses: 56 mg or 84 mg
    • Maintenance phase
  • Weeks 5-8
    • Administer Intranasally once weekly
    • 56 mg or 84 mg
  • Week 9 and after
    • Administer Intranasally every 2 Weeks or once weekly; individualize dosing frequency to the least frequent dosing to maintain remission/response
    • 56 mg or 84 mg

Major Depressive Disorder

Adult dosage

  • 84 mg twice per week x 4 weeks
  • May reduce dose to 56 mg twice per week based on tolerability
  • After 4 weeks of treatment, evaluate evidence of therapeutic benefit to determine the need for continued treatment

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”


Learn to Spot Depression: Symptoms, Warning Signs, Medication See Slideshow

What Are Side Effects Associated with Using Esketamine Intranasal?

Common side effects of Esketamine Intranasal include:

  • dissociation
  • feeling drunk,
  • increased blood pressure,
  • drowsiness, 
  • lack of energy,
  • dizziness, 
  • spinning sensation,
  • sedation,
  • feeling anxious,
  • nausea, 
  • vomiting, and
  • decreased sensations (touch or other senses).

Serious side effects of Esketamine Intranasal include:

  • extreme drowsiness or a light-headed feeling,
  • severe dizziness or feelings of floating,
  • unusual or unpleasant memories (flashbacks),
  • severe headache,
  • blurred vision,
  • pounding in the neck or ears, 
  • seizure,
  • chest pain,
  • problems with thinking or memory,
  • unusual changes in mood,
  • thoughts of hurting oneself,
  • worsening depression,
  • sleep problems,
  • hallucinations, feeling "spaced out", and
  • urination problems (painful urination, increased urination, urgent need to urinate).

Rare side effects of Esketamine Intranasal include:

  • none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Esketamine Intranasal?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

  • Esketamine Intranasal has severe interactions with no other drugs.
  • Esketamine Intranasal has serious interactions with the following drug:
  • Esketamine Intranasal has moderate interactions with at least 199 other drugs.
  • Esketamine Intranasal has minor interactions with no other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

What Are Warnings and Precautions for Esketamine Intranasal?


Effects of drug abuse

  • Physi/cal and psychological dependence
  • Long-term cognitive and memory impairment

Short-Term Effects

  • See “What Are Side Effects Associated with Using Esketamine Intranasal?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Esketamine Intranasal?”


  • Available only through a restricted access program (REMS)
  • Sedation is likely to occur
  • Dissociative or perceptual changes (including distortion of time, space, and illusions), derealisation, and depersonalization reported
  • The most common psychological effects are dissociative or perceptual changes (including distortion of time, space, and illusions), derealization, and depersonalization; carefully assess patients with psychosis before administering to determine if the benefit outweighs the risk
  • Because of the risk of sedation, dissociation, and increased blood pressure, patients must be monitored for at least 2 hours after each treatment session; carefully assess to determine if the patient is clinically stable and ready to leave the healthcare setting
  • Esketamine is a schedule III controlled substance and may be subject to abuse and diversion; assess risk for each patient before prescribing
  • Pooled analyses of placebo-controlled trials of antidepressant drugs have shown an increased risk for suicidality in patients aged below 24 years; monitor all patients receiving antidepressants, especially during the initial phase of treatment, for clinical worsening and emergence of suicidal thoughts and behaviors
  • Ulcerative or interstitial cystitis was reported with long-term, off-label use or misuse/abuse of ketamine; esketamine Intranasal showed a higher rate of lower urinary tract symptoms compared with placebo; however, no cases of interstitial cystitis were observed
  • It May cause fetal harm when administered to pregnant women
  • Cognitive impairment
    • Short-term
      • After a single dose in healthy volunteers, esketamine caused cognitive performance to decline 40 minutes postdose compared with placebo
      • Cognitive performance, mental effort, and sleepiness were comparable at 2 hours postdose
    • Long-term
      • Long-term cognitive and memory impairment reported with repeated ketamine misuse or abuse
      • No adverse effects were observed on ketamine Intranasal on cognitive functioning in a 1-year open-label safety study
      • Long-term cognitive effects have not been evaluated beyond 1 year
  • Drug interaction overview
    • No clinically significant interactions were observed when ketamine Intranasal was coadministered with CYP inducers, CYP3A inhibitors, CYP2B6 inhibitors, or substrates of CYP3A or CYP2B6
    • Coadministration with other CNS depressants may cause additive risk for sedation
    • Coadministration with psychostimulants or MAOIs may add to the risk of increased blood pressure

Pregnancy and Lactation

  • Not recommended during pregnancy
  • Based on published findings from pregnant animals treated with ketamine (a racemic mixture of arketamine and ketamine), may cause fetal harm when administered to pregnant women
  • Antidepressant registry: Healthcare providers are encouraged to register patients exposed to antidepressants during pregnancy at 1-844-405-6185 or
  • Clinical considerations
  • A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy
  • The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants
  • Consider the risk of untreated depression when discontinuing or changing treatment with antidepressants during pregnancy and postpartum
  • Contraception
    • Based on published animal reproduction studies, ketamine may cause embryo-fetal harm when administered to a pregnant woman
    • However, it is not clear how these animal findings relate to females of reproductive potential treated with the recommended clinical dose
    • Consider pregnancy planning and prevention for females of reproductive potential during treatment
  • Lactation
    • Esketamine is present in human milk; there are no data on the effects on the breastfed infant or milk production
    • Published studies in juvenile animals report neurotoxicity; because of the potential for neurotoxicity, advise patients that breastfeeding is not recommended during treatment


Depression is a(n) __________ . See Answer
Medscape. Esketamine Intranasal.

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